Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam

Abstract Background Malaria rapid diagnostic tests (RDTs) remain the main point-of-care tests for diagnosis of symptomatic Plasmodium falciparum malaria in endemic areas. However, parasites with gene deletions in the most common RDT target, histidine rich protein 2 (pfhrp2/HRP2), can produce false-n...

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Main Authors: Ngo Duc Thang, Eduard Rovira-Vallbona, Nguyen Thi Huong Binh, Dang Viet Dung, Nguyen Thi Hong Ngoc, Tran Khanh Long, Tran Thanh Duong, Nicholas J. Martin, Kimberly A. Edgel
Format: Article
Language:English
Published: BMC 2022-12-01
Series:Malaria Journal
Subjects:
Online Access:https://doi.org/10.1186/s12936-022-04399-w
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author Ngo Duc Thang
Eduard Rovira-Vallbona
Nguyen Thi Huong Binh
Dang Viet Dung
Nguyen Thi Hong Ngoc
Tran Khanh Long
Tran Thanh Duong
Nicholas J. Martin
Kimberly A. Edgel
author_facet Ngo Duc Thang
Eduard Rovira-Vallbona
Nguyen Thi Huong Binh
Dang Viet Dung
Nguyen Thi Hong Ngoc
Tran Khanh Long
Tran Thanh Duong
Nicholas J. Martin
Kimberly A. Edgel
author_sort Ngo Duc Thang
collection DOAJ
description Abstract Background Malaria rapid diagnostic tests (RDTs) remain the main point-of-care tests for diagnosis of symptomatic Plasmodium falciparum malaria in endemic areas. However, parasites with gene deletions in the most common RDT target, histidine rich protein 2 (pfhrp2/HRP2), can produce false-negative RDT results leading to inadequate case management. The objective of this study was to determine the prevalence of hrp2/3 deletions causing false-negative RDT results in Vietnam (Gia Lai and Dak Lak provinces). Methods Individuals presenting with malaria symptoms at health facilities were screened for P. falciparum infection using light microscopy and HRP2-RDT (SD Bioline Malaria Antigen Pf/Pv RDT, Abbott). Microscopically confirmed P. falciparum infections were analysed for parasite species by 18S rRNA qPCR, and pfhrp2 and pfhrp3 exon2 deletions were investigated by nested PCR. pfhrp2 amplicons were sequenced by the Sanger method and HRP2 plasma levels were determined by enzyme-linked immunosorbent assay (ELISA). Results The prevalence of false-negative RDT results among symptomatic cases was 5.6% (15/270). No pfhrp2 and pfhrp3 deletions were identified. False-negative RDT results were associated with lower parasite density (p = 0.005) and lower HRP2 plasma concentrations (p < 0.001), as compared to positive RDT. Conclusions The absence of hrp2/3 deletions detected in this survey suggests that HRP2-based malaria RDTs remain effective for the diagnosis of symptomatic P. falciparum malaria in Central Vietnam.
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spelling doaj.art-7db9907ad6c2436095410a4ba860ec0d2022-12-22T03:50:32ZengBMCMalaria Journal1475-28752022-12-012111810.1186/s12936-022-04399-wSurveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central VietnamNgo Duc Thang0Eduard Rovira-Vallbona1Nguyen Thi Huong Binh2Dang Viet Dung3Nguyen Thi Hong Ngoc4Tran Khanh Long5Tran Thanh Duong6Nicholas J. Martin7Kimberly A. Edgel8National Institute of Malariology, Parasitology and EntomologyVysnova PartnersNational Institute of Malariology, Parasitology and EntomologyNational Institute of Malariology, Parasitology and EntomologyNational Institute of Malariology, Parasitology and EntomologyVysnova PartnersNational Institute of Malariology, Parasitology and EntomologyU.S. Naval Medical Research Unit TWOU.S. Naval Medical Research Unit TWOAbstract Background Malaria rapid diagnostic tests (RDTs) remain the main point-of-care tests for diagnosis of symptomatic Plasmodium falciparum malaria in endemic areas. However, parasites with gene deletions in the most common RDT target, histidine rich protein 2 (pfhrp2/HRP2), can produce false-negative RDT results leading to inadequate case management. The objective of this study was to determine the prevalence of hrp2/3 deletions causing false-negative RDT results in Vietnam (Gia Lai and Dak Lak provinces). Methods Individuals presenting with malaria symptoms at health facilities were screened for P. falciparum infection using light microscopy and HRP2-RDT (SD Bioline Malaria Antigen Pf/Pv RDT, Abbott). Microscopically confirmed P. falciparum infections were analysed for parasite species by 18S rRNA qPCR, and pfhrp2 and pfhrp3 exon2 deletions were investigated by nested PCR. pfhrp2 amplicons were sequenced by the Sanger method and HRP2 plasma levels were determined by enzyme-linked immunosorbent assay (ELISA). Results The prevalence of false-negative RDT results among symptomatic cases was 5.6% (15/270). No pfhrp2 and pfhrp3 deletions were identified. False-negative RDT results were associated with lower parasite density (p = 0.005) and lower HRP2 plasma concentrations (p < 0.001), as compared to positive RDT. Conclusions The absence of hrp2/3 deletions detected in this survey suggests that HRP2-based malaria RDTs remain effective for the diagnosis of symptomatic P. falciparum malaria in Central Vietnam.https://doi.org/10.1186/s12936-022-04399-wMalariaPlasmodium falciparumDiagnosticsRapid Diagnostic TestHistidine rich protein 2Histidine rich protein 3
spellingShingle Ngo Duc Thang
Eduard Rovira-Vallbona
Nguyen Thi Huong Binh
Dang Viet Dung
Nguyen Thi Hong Ngoc
Tran Khanh Long
Tran Thanh Duong
Nicholas J. Martin
Kimberly A. Edgel
Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam
Malaria Journal
Malaria
Plasmodium falciparum
Diagnostics
Rapid Diagnostic Test
Histidine rich protein 2
Histidine rich protein 3
title Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam
title_full Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam
title_fullStr Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam
title_full_unstemmed Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam
title_short Surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic Plasmodium falciparum malaria patients in Central Vietnam
title_sort surveillance of pfhrp2 and pfhrp3 gene deletions among symptomatic plasmodium falciparum malaria patients in central vietnam
topic Malaria
Plasmodium falciparum
Diagnostics
Rapid Diagnostic Test
Histidine rich protein 2
Histidine rich protein 3
url https://doi.org/10.1186/s12936-022-04399-w
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